From knock-out models to role of important gene regions in vivo
Considerable effort and studies have been done on total gene knock-outs to understand physiological roles. While these are necessary, we need to transition to Phase 2 where models of alterations in individual regions of genes are made in vivo. For example, an important domain such as point mutation of a protein interaction domain, or DNA binding site or phosphorylation site. These will give more relevant mechanistic ...more »
Considerable effort and studies have been done on total gene knock-outs to understand physiological roles. While these are necessary, we need to transition to Phase 2 where models of alterations in individual regions of genes are made in vivo. For example, an important domain such as point mutation of a protein interaction domain, or DNA binding site or phosphorylation site. These will give more relevant mechanistic insights into development and diseases and are more relevant to diseases as you are more likely to see a single base alteration or a small deletion of an important region than a complete null. Further, the phenotypic outcome may be totally different than what the null studies may have pointed to, In this regard mutational screens or development of animal models based on identification of deleterious variants in human diseases may be helpful.
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